With stoppage-time added to the equation, Pompey had to play almost 90 minutes with just 10 men.
Joe Morrell was harshly dismissed by referee Samuel Barrott following a foul on Cameron Brannagan.
The score was level at 1-1 by that point, with Luke McNally’s opener quickly cancelled out by Michael Jacobs.
Ronan Curtis then put the 10-man visitors ahead, only for late strikes from Brannagan and Nathan Holland to leave them empty-handed.
Cowley was pleased with the efforts of his side, who battled valiantly throughout, but slammed the decision to dismiss Morrell.
The Blues boss said: “I’ve been a manager for a long time and I can’t remember a game where so much has gone against us, particularly from the referee.
“But I was proud of the players and their efforts. They fought heroically and put their bodies on the line.
“We got a good place in the game through a really nice counter-attacking goal and then defended for our lives.
"There are two players right in his line and he’s just guessed, so that’s unacceptable. I’ve got little faith in the system at the moment."
“It was going to take a brilliant strike to peg us back – and unfortunately for us, they got two of them from long-range.
“I’ve seen the red card back and it’s just not a sending off. Anyone who understands football will know that if the ball is high, the foot is high.
“The Oxford player’s head is no more than a metre from the floor and Joe’s just tried to help the ball on.
“Brannagan has ducked down into his foot, but the referee can’t even see it. Just look at his positioning.
“There are two players right in his line and he’s just guessed, so that’s unacceptable. I’ve got little faith in the system at the moment.
“On Monday when there was an offside decision missed in the lead up to the first goal, while this time the official’s management of the game was so below what’s expected at this level.
“You watch the Premier League and they’ve got VAR, but still can’t get it right, so what chance do we have!
“There’s not time for being victims, though, because we’ve got a game on Tuesday and have to get on with it.
“I’m just bitterly disappointed for our supporters – who were absolutely magnificent – and the players. I saw enough heart and will in the group to know we’ll come through.”